POS0015 EXPANSION OF NKP46+ INNATE LYMPHOID CELL IN THE JOINTS EXACERBATES COLLAGEN-INDUCED ARTHRITIS
Authors: J. Zhu, X. Liu, J. LI, S. Chen, L. Wu, R. Wang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> NK cells, a subset of innate lymphoid cells (ILCs), possessing both cytotoxicity and cytokine-producing properties, participate in many immune activities, e.g., control of viral infections, antitumor immunity, and autoimmune diseases. The role of innate Lymphoid cell (ILC) in rheumatoid arthritis remains controversial. <h3>Objectives</h3> This study investigates the alteration of NKp46+ ILC3-like cells in CIA mice over disease development in different tissues and possible association with the severity of arthritis. We further examined the role of NKp46+ ILC3-like cells cells via cell transfer and the receptor NKp46 via NKp46 knockout mice. <h3>Methods</h3> The percentage of NKp46+ ILC3-like cells in the peripheral blood, spleen, lymph nodes and inflamed paws from collagen-induced arthritis mice were examined through the disease progression. Correlation between the proportion of NKp46+ ILC3-like cells and subsets with arthritis score, histopathological changes, and bone destruction were evaluated. Adoptive cell transfer was performed to determine the effect of NKp46+ ILC3-like cells on arthritis development, and the role of receptor NKp46 was explored with NKp46 knockout mice. <h3>Results</h3> The percentage of NKp46+ ILC3-like cells in peripheral blood decreased at the late stage of the disease and negatively correlated with arthritis score. NKp46+ ILC3-like cells increased in the inflamed paws during arthritis development and were positively associated with arthritis score, histopathological change, and bone destruction. Adoptive transfer of NKp46+ ILC3-like cells before disease onset resulted in increased NKp46+ ILC3-like cells infiltration in the joints, higher incidence of arthritis, more severe clinical symptoms, and more pronounced joint inflammation and bone damage. NKp46 deficiency had no significant influence on the incidence and severity of arthritis in collagen-induced arthritis mice. <h3>Conclusion</h3> This study examined the proportion of NKp46+ ILC3-like cells cells in the peripheral blood, spleen, lymph nodes, and paw tissues in CIA mice and their correlation with disease severity. We confirmed that infiltration of NKp46+ ILC3-like cells cells in CIA joints positively correlates with arthritis progression, inflammation, cartilage erosion, and bone destruction. Most importantly, we revealed the pathogenic role of NKp46+ ILC3-like cells in rheumatoid arthritis through adoptive cell transfer, which prominently exacerbates CIA arthritis. NKp46 may not be the primary actor in the pathogenic function of NKp46+ ILC3-like cells in CIA. Overall, our current work suggests that NKp46+ ILC3-like cells infiltrate in inflamed joints and participate in the pathogenesis of autoimmune arthritis. <h3>Acknowledgements</h3> This study was supported by the Natural Science Foundation of China (No. 81803932 and 82174171). The funders had no role in study design, data collection, analysis, decision to publish, or manuscript preparation. <h3>Disclosure of Interests</h3> None Declared.